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Genome-Wide Analysis to Identify Pathways Affecting Telomere-Initiated Senescence in Budding Yeast

Lookup NU author(s): Dr Hsin Yu Chang, Dr Conor Lawless, Dr Stephen Addinall, Morgan Taschuk, Professor Anil Wipat, Professor Darren Wilkinson, Professor David Lydall

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

In telomerase-deficient yeast cells, like equivalent mammalian cells, telomeres shorten over many generations until a period of senescence/crisis is reached. After this, a small fraction of cells can escape senescence, principally using recombination-dependent mechanisms. To investigate the pathways that affect entry into and recovery from telomere-driven senescence, we combined a gene deletion disrupting telomerase (est1Δ) with the systematic yeast deletion collection and measured senescence characteristics in high-throughput assays. As expected, the vast majority of gene deletions showed no strong effects on entry into/exit from senescence. However, around 200 gene deletions behaving similarly to a rad52Δ est1Δ archetype (rad52Δ affects homologous recombination) accelerated entry into senescence, and such cells often could not recover growth. A smaller number of strains similar to a rif1Δ est1Δ archetype (rif1Δ affects proteins that bind telomeres) accelerated entry into senescence but also accelerated recovery from senescence. Our genome-wide analysis identifies genes that affect entry into and/or exit from telomere-initiated senescence and will be of interest to those studying telomere biology, replicative senescence, cancer, and ageing. Our dataset is complementary to other high-throughput studies relevant to telomere biology, genetic stability, and DNA damage responses.


Publication metadata

Author(s): Chang H, Lawless C, Addinall SG, Oexle S, Taschuk M, Wipat A, Wilkinson DJ, Lydall D

Publication type: Article

Publication status: Published

Journal: G3: Genes, Genomes, Genetics

Year: 2011

Volume: 1

Issue: 3

Pages: 197-208

Online publication date: 01/08/2011

Acceptance date: 01/06/2011

Date deposited: 16/11/2015

ISSN (electronic): 2160-1836

Publisher: Genetics Society of America

URL: http://dx.doi.org/10.1534/g3.111.000216

DOI: 10.1534/g3.111.000216

PubMed id: 22384331


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